Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy
Open accessAbstract
BACKGROUND: Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis. METHODS: In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein-Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS), in which higher scores indicate better health status. RESULTS: In the primary analysis, all-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P<0.001). Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a lower rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per year vs. 0.70 per year; 95% CI, 0.56 to 0.81). At month 30, tafamidis was also associated with a lower rate of decline in distance for the 6-minute walk test (P<0.001) and a lower rate of decline in KCCQ-OS score (P<0.001). The incidence and types of adverse events were similar in the two groups. CONCLUSIONS: In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo. (Funded by Pfizer; ATTR-ACT ClinicalTrials.gov number, NCT01994889 .).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Effective disease-modifying therapies are now available for selected SHD phenotypes-including obstructive HCM and transthyretin amyloid cardiomyopathy-so the clinical value of timely diagnosis has increased.
“Because effective disease-modifying therapies are now available for selected structural heart disease phenotypes—including obstructive HCM and transthyretin amyloid cardiomyopathy—the clinical value of timely diagnosis has increased.7,8”
From AI-ECG for Echocardiography Triage in Structural Heart Disease: Evidence, Implementation, and Future Directions (2026) · cites this paper as [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 34 · Cited by 2,857
Research works printed but not linked: 33
- Rapezzi C, Quarta CC, Riva L, et al. Transthyretin-related amyloidoses and the heart: a clinical overview. Nat Rev Cardiol 2010; 7: 398-408.
- Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation 2012; 126: 1286-300.
- Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of trans- thyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol 2016; 68: 161-72.
- Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyre- tin amyloidosis. Circulation 2016; 133: 2404-12.
- Castano A, Haq M, Narotsky DL, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: pre- dicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol 2016; 1: 880-9.
- González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection frac- tion. Eur Heart J 2015; 36: 2585-94.
- Castaño A, Narotsky DL, Hamid N, et al. Unveiling transthyretin cardiac amy- loidosis and its predictors among elderly patients with severe aortic stenosis under- going transcatheter aortic valve replace- ment. Eur Heart J 2017; 38: 2879-87.
- Damy T, Costes B, Hagège AA, et al. Prevalence and clinical phenotype of he- reditary transthyretin amyloid cardiomy- opathy in patients with increased left ven- tricular wall thickness. Eur Heart J 2016; 37: 1826-34.
- Grogan M, Scott CG, Kyle RA, et al. Natural history of wild-type transthyre- tin cardiac amyloidosis and risk stratifi- cation using a novel staging system. J Am Coll Cardiol 2016; 68: 1014-20.
- Blake CC, Geisow MJ, Oatley SJ, Rérat B, Rérat C. Structure of prealbumin: sec- ondary, tertiary and quaternary interac- tions determined by Fourier refinement at 1.8 A. J Mol Biol 1978; 121: 339-56.
- Monaco HL, Rizzi M, Coda A. Struc- ture of a complex of two plasma proteins: transthyretin and retinol-binding protein. Science 1995; 268: 1039-41.
- Colon W, Kelly JW. Partial denatur- ation of transthyretin is sufficient for amyloid fibril formation in vitro. Bio- chemistry 1992; 31: 8654-60.
- Castaño A, Drachman BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev 2015; 20: 163-78.
- Hammarström P, Schneider F, Kelly JW. Trans-suppression of misfolding in an amyloid disease. Science 2001; 293: 2459-62.
- Coelho T, Merlini G, Bulawa CE, et al. Mechanism of action and clinical applica- tion of tafamidis in hereditary transthyre- tin amyloidosis. Neurol Ther 2016; 5: 1-25.
- Maurer MS, Grogan DR, Judge DP, et al. Tafamidis in transthyretin amyloid cardiomyopathy: effects on transthyretin stabilization and clinical outcomes. Circ Heart Fail 2015; 8: 519-26.
- Rosenblum H, Castano A, Alvarez J, Goldsmith J, Helmke S, Maurer MS. TTR (transthyretin) stabilizers are associated with improved survival in patients with TTR cardiac amyloidosis. Circ Heart Fail 2018; 11(4): e004769.
- Maurer MS, Elliott P, Merlini G, et al. Design and rationale of the phase 3 ATTR-ACT clinical trial (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Circ Heart Fail 2017; 10(6): e003815.
- ATS Committee on Proficiency Stan- dards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: 111-7.
- Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Ques- tionnaire: a new health status measure for heart failure. J Am Coll Cardiol 2000; 35: 1245-55.
- Finkelstein DM, Schoenfeld DA. Com- bining mortality and longitudinal mea- sures in clinical trials. Stat Med 1999; 18: 1341-54.
- Wolfinger RD. An example of using mixed models and PROC MIXED for lon- gitudinal data. J Biopharm Stat 1997; 7: 481-500.
- Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clini- cal trials based on clinical priorities. Eur Heart J 2012; 33: 176-82.
- Coelho T, Maia LF, Martins da Silva A, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 2012; 79: 785- 92.
- Groenning BA, Nilsson JC, Sonder- gaard L, Fritz-Hansen T, Larsson HB, Hil- debrandt PR. Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure. J Am Coll Cardiol 2000; 36: 2072-80.
- Solomon SD, Foster E, Bourgoun M, et al. Effect of cardiac resynchronization therapy on reverse remodeling and rela- tion to outcome: Multicenter Automatic Defibrillator Implantation Trial: cardiac resynchronization therapy. Circulation 2010; 122: 985-92.
- Konstam MA, Rousseau MF, Kronen- berg MW, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventric- ular dysfunction in patients with heart failure. Circulation 1992; 86: 431-8.
- Sultan MB, Gundapaneni B, Schu- macher J, Schwartz JH. Treatment with tafamidis slows disease progression in early-stage transthyretin cardiomyopathy. Clin Med Insights Cardiol 2017; 11: 1179546817730322.
- Keohane D, Schwartz J, Gundapaneni B, Stewart M, Amass L. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid poly- neuropathy: additional supportive analy- ses from the pivotal trial. Amyloid 2017; 24: 30-6.
- Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc- pyrophosphate scintigraphy for differen- tiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Car- diovasc Imaging 2013; 6: 195-201.
- Haq M, Pawar S, Berk JL, Miller EJ, Ruberg FL. Can 99m Tc-pyrophosphate aid in early detection of cardiac involvement in asymptomatic variant TTR amyloido- sis? JACC Cardiovasc Imaging 2017; 10: 713-4.
- Glaudemans AW, van Rheenen RW, van den Berg MP, et al. Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloido- sis. Amyloid 2014; 21: 35-44.
- Galat A, Rosso J, Guellich A, et al. Usefulness of (99m)Tc-HMDP scintigra- phy for the etiologic diagnosis and prog- nosis of cardiac amyloidosis. Amyloid 2015; 22: 210-20.
- Authors
- Maurer, M. S., Schwartz, J. H., Gundapaneni, B., Elliott, P. M., Merlini, G., Waddington-Cruz, M., Kristen, A. V., Grogan, M., Witteles, R., Damy, T., Drachman, B. M., Shah, S. J., Hanna, M., Judge, D. P., Barsdorf, A. I., Huber, P., Patterson, T. A., Riley, S., Schumacher, J., Stewart, M., Sultan, M. B., & Rapezzi, C.
- Affiliations
- St Bartholomew's Hospital (GB)
- From the Columbia University Vagelos College of Physicians and Surgeons (M.S.M.) and Pfizer (J.H.S., A.I.B., P.H., J.S., M.B.S.), New York; Syneos Health, Raleigh, NC (B.G.); University College London and St. Bartholomew’s Hospital, London (P.M.E.); the Amyloidosis Center, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, and the University of Pavia, Pavia (G.M.), and the Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna (C.R.) —...
- Northwestern University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-09-13
- Volume
- 379
- Issue
- 11
- Pages
- 1007-1016
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2888036721
- Cited by
- 2,857
- References
- 34
- Citations by year
- 2026: 371 · 2025: 468 · 2024: 441 · 2023: 322 · 2022: 328 · 2021: 349 · 2020: 319 · 2019: 222 · 2018: 33 · 2017: 1
- FWCI
- 82.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, other-oa)
- Funders
- Pfizer, Inc.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- tafamidis, transthyretin amyloid cardiomyopathy, transthyretin stabilization, amyloid fibril formation, all-cause mortality, cardiovascular hospitalization, functional capacity, health-related quality of life, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, drug safety and tolerability, variant transthyretin
- MeSH terms
- Walk Test, Administration, Oral, Aged, Aged, 80 and over, Benzoxazoles, Double-Blind Method, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Cardiomyopathies, Prealbumin, Quality of Life, Survival Analysis, Disease Progression, Amyloid Neuropathies, Familial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
